Severe Combined Immunodeficiency
Disease Details
Family Health Simplified
- Description
- Severe Combined Immunodeficiency (SCID) is a genetic disorder characterized by a severe defect in both the T- and B-lymphocyte systems, leading to extreme vulnerability to infections.
- Type
- Severe Combined Immunodeficiency (SCID) is a type of primary immunodeficiency disorder. It is primarily transmitted through X-linked recessive inheritance. However, autosomal recessive forms also exist.
- Signs And Symptoms
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Severe Combined Immunodeficiency (SCID) is characterized by a markedly defective immune system. Signs and symptoms typically present in infancy and may include:
1. Frequent, severe infections: These can be bacterial, viral, or fungal and are often more serious than in individuals with a normal immune system.
2. Failure to thrive: Poor growth or inability to gain weight and grow at the expected rate.
3. Chronic diarrhea: Persistent and severe diarrhea.
4. Skin rashes: Often resembling eczema.
5. Oral thrush: A fungal infection in the mouth.
6. Respiratory issues: Including pneumonia which may be recurrent.
Early diagnosis and treatment are critical for managing SCID, as the condition can be life-threatening. Treatment options typically involve immune system restoration, such as bone marrow or stem cell transplantation. - Prognosis
- Severe Combined Immunodeficiency (SCID) prognosis varies depending on early diagnosis and treatment. Without treatment, SCID is typically fatal within the first year of life due to severe infections. However, with early interventions such as bone marrow transplants, gene therapy, and enzyme replacement therapy, the prognosis significantly improves, and many children can lead relatively normal lives.
- Onset
- Severe Combined Immunodeficiency (SCID) typically has an onset in infancy, usually within the first few months of life.
- Prevalence
- The prevalence of Severe Combined Immunodeficiency (SCID) is estimated to be about 1 in 50,000 to 100,000 live births. This condition is a rare, genetic disorder characterized by a severely compromised immune system.
- Epidemiology
- The most commonly quoted figure for the prevalence of SCID is around one in 100,000 births, although this is regarded by some to be an underestimate of the true prevalence; some estimates predict that the prevalence rate is as high as one in 50,000 live births. A figure of about one in 65,000 live births has been reported for Australia.Due to the particular genetic nature of SCID, a higher prevalence may be found in certain regions and associated cultures where higher rates of consanguineous mating occur (i.e. mating between blood relatives). A Moroccan study reported that consanguineous parenting was observed in 75% of the families of Moroccan SCID patients.Recent studies indicate that one in every 2,500 children in the Navajo population inherit severe combined immunodeficiency. This condition is a significant cause of illness and death among Navajo children. Ongoing research reveals a similar genetic pattern among the related Apache people.
- Intractability
- Severe Combined Immunodeficiency (SCID) is generally considered intractable if left untreated. However, with advancements in medical treatments such as hematopoietic stem cell transplantation (HSCT), gene therapy, and enzyme replacement therapy, it is now possible to effectively manage and potentially cure the condition. Early detection and treatment are crucial for a positive outcome.
- Disease Severity
- Severe Combined Immunodeficiency (SCID) is an extremely severe disease. It is a life-threatening condition characterized by a significantly impaired immune system, making affected individuals highly susceptible to infections. If untreated, it generally leads to death within the first year or two of life.
- Healthcare Professionals
- Disease Ontology ID - DOID:627
- Pathophysiology
- Severe Combined Immunodeficiency (SCID) is a group of rare, inherited disorders characterized by profound defects in both T- and B-lymphocyte function, leading to severe immunodeficiency. The pathophysiology involves genetic mutations that affect various aspects of lymphocyte development and function. This results in a marked reduction or absence of T cells, which impairs cellular immunity, and often a subsequent reduction or dysfunction of B cells, compromising humoral immunity. Common genetic mutations associated with SCID include those in the IL2RG, JAK3, RAG1, RAG2, and ADA genes, among others. Without functional immune cells, individuals with SCID are highly susceptible to infections and typically present within the first few months of life with recurrent, severe infections.
- Carrier Status
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Severe Combined Immunodeficiency (SCID) is typically inherited in an X-linked or autosomal recessive pattern. Carrier status varies based on the type of SCID:
1. **X-linked SCID:** Mostly affects boys. Females with one mutated allele on the X chromosome are carriers but usually do not show symptoms.
2. **Autosomal Recessive SCID:** Both males and females can be carriers if they have one mutated allele of a relevant gene (e.g., ADA, RAG1, RAG2). Carriers generally do not exhibit symptoms but have a 25% chance of passing the condition to offspring if both parents are carriers.
Carrier status can be determined through genetic testing. - Mechanism
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Severe Combined Immunodeficiency (SCID) is a group of rare genetic disorders characterized by a profound defect in both T- and B-lymphocyte function, leading to severe immune system dysfunction.
### Mechanism
Individuals with SCID have a severely compromised immune system, which leaves them highly susceptible to infections. The hallmark of SCID is the lack of functional T and B cells, crucial components of the adaptive immune system.
### Molecular Mechanisms
- **Genetic Mutations**: SCID can result from mutations in various genes that are critical for the development and function of immune cells. Some common genetic mutations associated with SCID include:
- Mutations in the IL2RG gene, which encodes the common gamma chain (γc) shared by multiple interleukin receptors. This is the most common cause and is known as X-linked SCID.
- Mutations in the ADA gene, which encodes adenosine deaminase. A deficiency in this enzyme leads to the accumulation of toxic metabolites that are particularly harmful to lymphocytes.
- Mutations in the RAG1 and RAG2 genes, which are essential for the recombination of antigen receptor genes in T and B cells.
- Mutations in JAK3, which is involved in signaling through the common gamma chain.
These genetic defects disrupt critical pathways in the development, maturation, and function of T and B lymphocytes, leading to severe immunodeficiency. As a result, patients with SCID are unable to effectively fight off infections from bacteria, viruses, and fungi, ultimately making even minor infections potentially life-threatening. - Treatment
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The most common treatment for SCID is bone marrow transplantation, which has been very successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. The half-matched type of transplant is called haploidentical. Haploidentical bone marrow transplants require the donor marrow to be depleted of all mature T cells to avoid the occurrence of graft-versus-host disease (GVHD). Consequently, a functional immune system takes longer to develop in a patient who receives a haploidentical bone marrow transplant compared to a patient receiving a matched transplant. The first reported case of successful transplant was a Spanish child patient who was interned in Memorial Sloan Kettering Cancer Center in 1982, in New York City. David Vetter, the original "bubble boy", had one of the first transplantations also, but eventually died because of an unscreened virus, Epstein-Barr (tests were not available at the time), in his newly transplanted bone marrow from his sister, an unmatched bone marrow donor. Today, transplants done in the first three months of life have a high success rate. Physicians have also had some success with in utero transplants done before the child is born and also by using cord blood which is rich in stem cells. In utero transplants allow for the fetus to develop a functional immune system in the sterile environment of the uterus; however complications such as GVHD would be difficult to detect or treat if they were to occur.More recently gene therapy has been attempted as an alternative to the bone marrow transplant. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. In 1990, four-year-old Ashanthi DeSilva became the first patient to undergo successful gene therapy. Researchers collected samples of DeSilva's blood, isolated some of her white blood cells, and used a retrovirus to insert a healthy adenosine deaminase (ADA) gene into them. These cells were then injected back into her body, and began to express a normal enzyme. This, augmented by weekly injections of ADA, corrected her deficiency. However, the concurrent treatment of ADA injections may impair the success of gene therapy, since transduced cells will have no selective advantage to proliferate if untransduced cells can survive in the presence of the injected ADA.
In 2000, a gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients have developed leukemias. Work aimed at improving gene therapy is now focusing on modifying the viral vector to reduce the likelihood of oncogenesis and using zinc-finger nucleases to further target gene insertion. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the gamma c gene that may be oncogenic when expressed by a retrovirus.
From the treatments of Ashanthi DeSilva in 1990, which is considered gene therapy's first success until 2014, around 60 patients were treated for either ADA-SCID or X-SCID using retroviruses vectors. As previously mentioned, the occurrence of leukemia cases forced researchers to make changes to improve safety. In 2019, a new method using an altered version of the HIV virus as a lentivirus vector was reported in the treatment of eight children with X-SCID, and in 2021 the same method was used in 50 children with ADA-SCID, obtaining positive results in 48 of them.There are also some non-curative methods for treating SCID. Reverse isolation involves the use of laminar air flow and mechanical barriers to avoid physical contact with others in order to isolate the patient from any harmful pathogens present in the external environment. Another non-curative treatment for patients with ADA-SCID is enzyme replacement therapy, in which the patient is injected with polyethyleneglycol-coupled adenosine deaminase (PEG-ADA), which metabolizes the toxic substrates of the ADA enzyme and prevents their accumulation. Treatment with PEG-ADA may be used to restore T cell function in the short term, enough to clear any existing infections before proceeding with curative treatment such as a bone marrow transplant. - Compassionate Use Treatment
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Severe Combined Immunodeficiency (SCID) is a rare genetic disorder characterized by a severely compromised immune system. For compassionate use and off-label or experimental treatments, here are some options:
1. **Gene Therapy**: Experimental gene therapy has shown promise in some cases of SCID, particularly for those with ADA-SCID and X-linked SCID. This involves inserting a normal copy of the defective gene into the patient’s own stem cells.
2. **Enzyme Replacement Therapy**: For ADA-SCID, enzyme replacement therapy with pegademase bovine (PEG-ADA) can be used to replace the deficient enzyme.
3. **Hematopoietic Stem Cell Transplantation (HSCT)**: Although not experimental, HSCT from a matched sibling donor or a matched unrelated donor is a standard treatment. Haploidentical transplants (from a partially matched family member) or cord blood transplants are used when matched donors aren't available.
4. **Interleukin-2 (IL-2) Therapy**: This cytokine has been used in experimental settings to enhance immune function in some SCID patients.
5. **Experimental Pharmacotherapy**: Various immunomodulatory drugs are under investigation to support immune function or correct the underlying genetic defects.
For any experimental treatment, participation in clinical trials or compassionate use programs typically requires specific criteria and oversight by medical professionals. - Lifestyle Recommendations
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For severe combined immunodeficiency (SCID), lifestyle recommendations focus on preventing infections and maintaining overall health. Here are some key points:
1. **Avoid Exposure to Infections**:
- Limit contact with sick individuals.
- Avoid crowds and public spaces during high infection periods.
- Do not use live vaccines or be in close proximity to individuals who have received them.
2. **Maintain a Clean Environment**:
- Ensure cleanliness in living spaces.
- Practice frequent handwashing with soap and water.
- Regularly disinfect commonly touched surfaces.
3. **Nutritional Support**:
- Follow a balanced and nutritious diet to support overall health.
- Work with healthcare providers to ensure adequate intake of essential vitamins and minerals.
4. **Specialized Care**:
- Regular doctor visits for monitoring health and early detection of potential issues.
- Strict adherence to prescribed medical treatments and interventions.
- Consideration for hematopoietic stem cell transplantation or gene therapy if recommended by healthcare providers.
5. **Protective Measures**:
- Use protective masks and gloves when necessary.
- Implement safe food handling practices to avoid foodborne illnesses.
6. **Mental and Emotional Well-being**:
- Support mental health through counseling or support groups.
- Engage in activities that promote a positive outlook and emotional resilience.
These recommendations should be tailored to individual needs in consultation with healthcare providers. - Medication
- Severe Combined Immunodeficiency (SCID) primarily requires treatment through hematopoietic stem cell transplantation (HSCT) to provide the patient with a functioning immune system. Enzyme replacement therapy, such as with polyethylene glycol-modified adenosine deaminase (PEG-ADA), can be used for adenosine deaminase deficiency-related SCID. Gene therapy is also an emerging treatment option, showing promise in correcting genetic defects causing SCID. Medications to manage infections and prophylactic antibiotics, antifungals, and antivirals are used to protect SCID patients from opportunistic infections.
- Repurposable Drugs
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Severe Combined Immunodeficiency (SCID) is typically treated with bone marrow or stem cell transplantation. However, some drugs originally developed for other conditions are being explored for repurposing in SCID treatment:
1. **Interleukin-2 (IL-2):** Initially developed for cancer and viral infections, IL-2 helps boost immune system function and may support immune recovery in SCID patients.
2. **Pegademase Bovine (Adagen):** Originally devised for enzyme replacement therapy in ADA-deficient SCID, a specific form of SCID.
3. **Janus Kinase (JAK) Inhibitors:** Drugs like Ruxolitinib, typically used for myeloproliferative disorders, have potential for reducing inflammation and promoting immune reconstitution.
These drugs are still under investigation and are not yet standard treatment for SCID. - Metabolites
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For Severe Combined Immunodeficiency (SCID), there are no specific metabolites directly associated with the disease itself. SCID is a group of primary immunodeficiency disorders characterized by the disturbed development of functional T cells and B cells, caused by various genetic defects. However, due to the nature of the disease affecting the immune system, patients may exhibit secondary metabolic disturbances or infections that could affect metabolite profiles.
If there is something specific you are looking for related to metabolites in SCID, please provide more details. - Nutraceuticals
- Nutraceuticals, often dietary supplements or foods with health benefits, do not provide specific treatment for Severe Combined Immunodeficiency (SCID). SCID is a genetic disorder characterized by a severely impaired immune system, usually requiring medical interventions such as bone marrow transplants, gene therapy, or enzyme replacement therapy. Nutraceuticals cannot address the fundamental genetic defects or restore immune function in SCID patients.
- Peptides
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Severe Combined Immunodeficiency (SCID) is a group of rare, inherited disorders characterized by a severely compromised immune system. Regarding peptides and nanotechnology in SCID, research is ongoing to explore novel therapeutic strategies:
1. **Peptides**:
- Peptide-based vaccines and therapies are being investigated for their potential to enhance immune response or correct dysfunctional pathways.
- Certain synthetic peptides might be used to deliver therapeutic genes or molecules to correct genetic defects causing SCID.
2. **Nanotechnology**:
- Nanoparticles can be utilized to deliver genes or drugs precisely to target cells, potentially correcting the underlying genetic defects in SCID.
- Nano-based delivery systems can enhance the efficacy and reduce the side effects of treatments like gene therapy.
These advanced therapeutic strategies aim to improve treatment outcomes for SCID patients by addressing the underlying genetic causes more effectively.